Recent work with cultured mammalian cells indicates that the capacity for active Na/K transport increases in response to partial inhibition of this transport system. I propose to combine the approaches of ion transport physiology and somatic cell genetics to investigate the changes in Na/K transport in cultured Chinese hamster ovary cells (CHO) exposed to low (K) medium. I will study the transport capacity during a 72 h low (K) treatment. Tracer flux measurements will be used to determine if there are changes in the Na:K coupling ratio and/or the kinetic parameters of K influx, Vmax and Km. Also, changes in the density of Na/K pumps will be estimated by measuring the activity of Na,K-ATPase in the cell membranes. These data will be used to determine if there is an increase in the synthesis of Na/K pump (i.e., induction) and whether or not other transport parameters change in response to low (K) treatment. Additional low (K) resistant variants will be isolated and utilized to explore the variety of mechanisms which can produce this phenotype. I plan to isolate a variant which is temperature sensitive for the ability to recover transport capacity during low (K) treatment. This type of variant will be used to investigate further into the metabolic mechanisms involved in this compensatory response. Also, I hope to isolate variants which are temperature sensitive for Na/K transport in normal medium. A series of these variants will facilitate greatly an initial investigation into the metabolic steps of the steady-state biosynthesis of the Na/K pump.